The newest research about living with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (ME/CFS)/fibromyalgia, with personal observations
(the most pertinent parts of long articles will be highlighted for the reader)

About The Author

On March 4, 1988, I was diagnosed with Post-Viral Syndrome, which CDC soon decreed had to be referred to by the silly name "Chronic Fatigue Syndrome". My symptoms definitely traced back to a severe flu-like illness with a 105 fever for several days in mid-February 1987.
Despite relapses and increasing symptoms, I continued to work full-time as a legal secretary/paralegal -- even when I had no Quality of Life because I had to spend every non-working hour in bed so I could work the next day -- until February 2000, when months of severe sleep disturbance and ever-increasing symptoms (due to sleeping 2 hours or less a night due to the pain) cost me my job.
The doctors and judge didn't want to hear about failed attempts to return to work; they just assumed I don't want to work. "Don't confuse me with facts, my mind is already made up."
Since ADA will not force an employer to provide the accommodations I need, I started my own business so I could lie down whenever I needed to. I do proofreading and editing from home.
Visit www.CFSfacts.org or CFS Facts at YahooGroups or on Facebook if you want to learn the truth behind the myths.

Followers

Tuesday, March 18, 2008

Image caption: "The stigma associated with the disease can sometimes be asmuch of a problem as the symptoms."

Last Updated: 12:01am GMT 18/03/2008

A simple blood test may revolutionise the way we treat patients with ME,reports Bob Ward

British researchers are close to developing, for the first time, a bloodtest and potential drug treatments for myalgic encephalomyelitis (ME), alsoknown as chronic fatigue syndrome (CFS), following groundbreaking work onits genetic origins.

ME/CFS affects about one in 200 people, and women sufferers outnumber men bysix to one. It causes a constant feeling of extreme exhaustion and malaisefor more than six months, along with sleep abnormalities, memory andconcentration difficulties and a great deal of pain.

In its most extreme form, the disease leaves sufferers bed-ridden and caneven be fatal.

But patients now have new hope, thanks to research published in the Journalof Clinical Pathology by Dr Jonathan Kerr of St George's University ofLondon and his colleagues.

They have identified 88 genes that produce different levels of proteins and other molecules in ME/CFS sufferers compared with the rest of the population.

Dr Kerr's team carried out a complex analysis of the records of 55 patientsand found that they could be divided into seven sub-types according to thespecific gene combinations found in their white blood cells, and theseverity of their symptoms.

The most acutely affected patients had 71 of the 88 gene abnormalities.

The results of this work should allow better understanding of the causes anddevelopment of the disease. Many of the genes are known to be affected when a person contracts a virus, a factor which is believed to trigger many cases of ME/CFS.

Importantly, the researchers also recognised that five of the 88 genes aretargeted by drugs which are already used to treat other diseases.

The team is now investigating whether the faulty genes produce abnormallevels of proteins that can be detected as minute quantities of "biomarkers"in the blood of patients.

"If proven to be sensitive and specific indicators of the illness, thediscovery of protein biomarkers could lead to the development of adiagnostic test for ME/CFS, which would revolutionise our approach to thisdisease," explains Dr Kerr.

He will present his results at a conference on ME/CFS biomedical research inCambridge in May.

The research may even lead to a change in attitudes to the disease, often trivialised as "yuppie flu".

Sarah, 31, who was diagnosed with ME/CFS two years ago, says: "The stigmaassociated with the disease can sometimes be as much of a problem as thesymptoms.

"Some think that it is 'all in the mind' and can be cured by a good night'ssleep. It can be difficult to get friends and work colleagues to understandjust how difficult it is to live with a disease that is so debilitating butvirtually invisible."

Attitudes among funders of medical research also need to change, says Dr Neil Abbot, operations director at the charity ME Research UK. "Studies on the psychological aspects of ME/CFS seem to have vacuumed up attention and funding at the expense of hard-core biomedical studies," he says.

"Most of the £3 million spent by the Medical Research Council on the illnessin the last six years has gone towards projects on the psychologicalmanagement of the disease, while there is evidence that around 30applications, some from established biomedical research groups, have notbeen funded."

The work carried out by Dr Kerr and his colleagues is funded by a smallcharity, the CFS Research Foundation, which was set up in 1993 by a group ofdoctors and scientists who were concerned about the direction and quality ofwork on the disease.

Its director, Anne Faulkner, is optimistic about the search for a cure: "Webelieve that this disease can and will be conquered, but it will need thededicated work of distinguished research scientists and the determination ofpeople in the community to bring this about."

Bob Ward has donated the fee for this article to the CFS ResearchFoundation (www.cfsrf.com ) and ME Research UK (www.meresearch.org.uk ). He isformer winner of the Bayer/Telegraph science writer award, judged by a panelthat includes Sir David Attenborough and Adam Hart-Davis, which is now opento 15-year-olds too. The closing date is March 31. See science-writer.co.uk for details

* * *

One more nail in the coffin of those crackpots who call us lazy and crazy because they cannot accept the notion that this is a serious physical ailment caused by a virus and not just a personality flaw.

Go ahead, have one last laugh at our expense, because when this is proven it's going to be those people who are called crazy for denying the reality for so long in the face of 5000+ research studies proving objective medical abnormalities in True CFS patients. The stupidity and stubbornness of the detractors always amazes me ... they can't accept that maybe they were wrong.

I am mortified to have to tell everyone that the petition website where the petition to adopt the Canadian (international) consensus document in the United 'States has been housed is - well, in my opinion, wholly unethical and I have had to take the petition down.

After about two weeks, and without warning me, the company running the website inserted a request for funding for THEM! I learned that people would sign the petition, and as soon as they did that, the website would shift to one with different amounts of donations listed - and one person who vetted it for me said that they already had the amount checked and it didn't seem to be uncheckable.

Every type of dispicable practice on internet seems legal. They probably buried this in fine print somewhere.

I want to assure ANYONE who signed that petition and then got asked to donate money that:

**** The money did not go to me or to M.E. or CFS advocacy. It went to the website company. ****

Perhaps we can circulate a petition the old-fashioned way, getting signatures wherever people gather. This was a most disheartening experience.

People have the notion that CFS means you’re depressed and sleep 20-24 hours a day. That’s not necessarily accurate.

When the virus is active, yes, like anyone who has the flu, you’ll sleep a lot because having a virus is exhausting. Being sick wears down your body, and sleeping a lot helps you get well.

But when you’re not actively sick/fighting the virus, it’s just as likely that you’re not sleeping well. When this relapse started, I was going to bed as early as 8 PM, but tossing and turning until 5 or 6 AM before finally getting an hour or two of sleep before I had to get up to go to work. Insomnia is a recognized symptom – common enough to have a nickname "tired and wired", you’re exhausted enough to collapse into bed, but still can’t get to sleep.

Unfortunately, I ran into a doctor who couldn’t differentiate between "time spent in bed" and "time spent asleep"; according to him, the amount of time I spent in bed proved I was getting plenty of sleep and didn’t need a sleeping pill to help me sleep. It was not until I found a doctor who knew how to listen, who actually heard the part about actually sleeping only an hour or two out of the many hours that I spent in bed, that I got sleeping pills to stop the deterioration.

Ordering a sleep study would have given that first doctor the proof that I wasn’t imagining things, I wasn’t exaggerating, but because he didn’t know that CFS is neither laziness nor depression, he simply assumed that he knew better than I did what went on at my house at 3 AM and revised my reporting to match what he wanted to hear. I knew I was awake all night because I was in another room knitting scarves, reading books, sending e-mails; he was just as adamant that I was actually in bed sleeping, and just convincing myself that if I looked at the clock at 2 AM and looked at the clock at 4 AM, I "thought" I was awake from 2-4 when really I’d slept most of the intervening 2 hours. My evidence that I had not been asleep wasn’t what he wanted to hear, so he convinced himself – and tried to convince me – that I was confused about how much I was sleeping and when.

Then he set out to convince me that the reason I couldn’t sleep at night was because I was napping during the day; that might have been the case after I lost my job, but when the problem started, I was in an office all day and someone would have noticed if I had been sleeping at my desk. But, it was a pat answer that could let him put the blame on my sleep habits rather than searching further for the root cause, solving the pain puzzle that was actually to blame for keeping me awake all night.

Eventually, I got into a clinical trial for an experimental sleeping pill. Step one was to fill out a detailed Sleep Diary, recording each night what time I went to bed, what time I fell asleep, how many times I woke up during the night, how much time I spent awake during the night, what time I woke up, with or without an alarm clock waking me. With documentation showing that level of specificity, it became apparent to the doctor running the trial that I was not exaggerating ... I had what was classified as a severe sleep disturbance, averaging 2 hours sleep a night. He asked the right questions, and got the responses that helped him to see that I was functioning because I was able to nap during the day, bringing me up to 4-6 hours of sleep in a 24-hour period. If I had a job during the day, I wouldn't be functioning because I wouldn't get those naps essential to keeping me going.

Whereas the other doctor added up the hours I spent in bed to conclude that I was sleeping excessively (which is what his desired diagnosis of depression required him to see), this doctor concluded that I was probably tired all the time because I was seriously sleep deprived despite spending a lot of time in bed trying to fall asleep. Part of the commitment for the clinical trial was avoiding daytime naps; sure enough, when I was getting 7-8 hours of good sleep at night, I had no need to nap during the daytime because I was well-rested: I could lie down during the day because I felt faint and had no urge to go to sleep even though I was lying in bed.

When I was immediately back to 2 hours a night every time I went on placebo, it became apparent that the problem was not "poor sleep hygiene" or "a need to retrain yourself to sleep at night" – the months spent on the actual drug should have re-set my body clock if that were the only problem. But I could tell the very first night of each pack of pills whether I was on Study Drug or on placebo; the effects were that dramatic: on Study Drug I fell asleep in 15 minutes, on placebo I tossed and turned till 5 AM. For a full year in that clinical trial, I went to bed at the same time, took the pill at the same time and got up at the same time, exactly what you’re supposed to do to correct a sleep hygiene problem. Yet, even after a year of carefully-documented good sleep hygiene, I could not fall asleep until 5 AM without the magic pills, and we knew that was not just "placebo effect" because I’d had the same reaction when I was taking the placebos.

My first specialist in 1988 had told me the key to recuperation was to ensure the patient was getting good quality sleep – someone who sleeps badly 20 hours a day may only be getting the equivalent of 3 hours of good sleep. If you look at it that way, it’s no wonder CFS patients are tired; you’d be, too, if you were living on 3 hours of sleep for months or years on end.

Researchers have found a variety of problems that prevent CFS patients from getting the deep sleep they need. If you can get the patient into deep sleep, their body begins to heal itself. It’s not a full cure, the cause of CFS is more than just sleep deprivation, but better sleep will improve your immune function, which will allow your body to get the upper hand over the virus. I’ll never be rid of the virus, but if my immune system is working I can keep the virus in check so I’m not deathly ill, just "inconvenienced" -- before getting on sleeping pills, I caught everything that came down the pike; now I'm not constantly sick with every cold/flu/bug that's going around, though when I catch something, I'm still sick a lot longer than a healthy person would be.

Unfortunately, too many CFS patients run into doctors who don’t understand the difference between quantity and quality, and like my doctor, believe that "there was no need for a sleeping pill, you were already sleeping too much" without taking into account that bad quality sleep is going to require much more time to achieve the same recharging results.

Ordering a sleep study right off would have saved me years of agony and proved that I knew what I was talking about when I said the problem was easily solved with sleeping pills (or at least pain pills that would let me get to sleep) so that I could get a reasonable amount of sleep each night.

Since the Disability judge has the same notion that I’m just lazy and depressed and sleeping my life away, I’ve taken to noting in my symptom diary that I "spent 12 hours in bed, only 3 of it actually asleep", or that although I slept till noon, the fact that I didn’t fall asleep till 6 AM means that I am not sleeping excessively ... 6 hours of sleep is a perfectly reasonable amount of sleep for a 24-hour period, I just was not able to force myself to fall asleep at a normal hour. Falling asleep is related to cortisol level, and research has shown a cortisol problem in CFS patients.

Now that the virus is no longer running rampant, I don’t need a lot of sleep to deal with the system overload caused by fighting the virus. But, like everyone else, I do need to get a good night’s sleep to feel my best, and 2-3 hours a night doesn’t cut it. If I haven’t fallen asleep till dawn, then, for the sake of my health, I need to get 6-8 hours even if it looks like laziness to other people that I therefore don’t get up till noon.

I once had a boss who was definitely a Morning Person. He’d bound out of bed at 4 AM and be at his desk before 6. I’d stagger in at 8:30 with my eyes half-open and barely functioning. The only explanation he could imagine was that I was lazy. Well, then we had to do trial prep. At 5 PM, he was lagging, and I was just hitting my stride. At 8 PM, he was ready for bed, and I was in top gear. When he left at 11 PM, he was half-dead, and I was just getting my second wind, cheerily assuring him that I would finish up, no problem. He looked like I’d totally flipped when I said "it’s not that late" and dove back into the pile. The computer-generated times on the last documents showed that I was still there after 2 AM. He did the math ... I’d just put in an 18-hour day without complaining, and was there on time the next morning (i.e., I’d gotten less than 5 hours sleep). He finally understood: I’m not lazy, I’m an Owl. My body clock runs on an entirely different schedule than his. Doing trial prep, he could see that there were times of day that the situation was reversed: he was the one who was half-asleep and I was working all-out. He apologized for thinking badly of me; he had never seen me operating at full speed, because I didn’t reach my peak during normal business hours.

In the same way, if people had the actual facts, and not just their erroneous assumptions about CFS, they would be less likely to make disparaging remarks. I’d like to see one of the people who calls me "lazy" and "unwilling to work" continue to function at work after months of sleeping only 2 hours a night; they’d probably give up long before I did.

Someone who hated their job and was always looking for a reason to quit will never understand that some of us loved our jobs, planned to work until we died, and never had any intention of giving up our careers for husbands, kids, or even a winning Lotto ticket. It’s been my experience that those who are willing to manipulate a spouse to avoid having to hold a job simply cannot grasp that this is not the goal of every human being; there’s a comic strip on my fridge that says something about "you know you’ve found the right job when you’d be willing to do it for free", and that’s how I felt about my paralegal job. It broke my heart to be told that I would never return to the work I loved.

I have finally found a job that uses my skills and education, but allows me to work during my most functional hours, i.e., after 5 PM. How many of the detractors are still working at midnight? I often am. But, like my Morning Person boss, they can’t fathom that it’s not laziness, just that some people find it more natural to go to bed late and wake up late. (I was raised in a family of nightowls; an old friend and I once went out for the evening and when we got home before midnight, my mom’s first reaction was that if we were home that early, one of us had to be sick. To me and my family – some of whom worked nights their whole career – it’s equally weird that some grown-ups go to bed before 10 PM. But we would never be so rude as to call them names because they run out of gas long before we do.) I have known for 30 years that I get my best sleep after 6 AM, but the business world doesn’t care; they expected me to get up just as I was hitting the most recuperative sleep phase.

Nowadays, without the physically-exhausting task of fighting the virus, I’m sleeping a reasonable number of hours a day – rarely more than 8 – even though it’s not on the same schedule as most people. Dr. Murphree suggests that it takes at least one year of good sleep to make up for each year of bad sleep, so I still have a ways to go to reach maximum improvement. Maybe in a couple years I’ll be back to working circles around most people, when I’m allowed to work in harmony with my natural sleep schedule. (By some measures, I already am ... when my back-up was doing this job as a full-time employee in an agency office, she had a daily minimum quota that she had to meet; the other night, I did the number of pages that her boss considered 8 hours of work in just over 2 hours.)

Whatever your reasons for verbally abusing CFS patients, let me assure you that calling them "lazy" and making jokes about them "sleeping all day" proves only that you don’t have a clue what CFS really is. You clearly saw the word "fatigue" and jumped to conclusions without ever reading further to learn about the virus, the neurological aspects, the immune system dysfunction, the cardiomyopathy, and all the other problems that go far beyond your fantasy of spending the day on the couch, eating bonbons and watching soap operas. There’s no fantasy in the reality of spending the day on the toilet, having to morning, noon and night eat the one and only food that doesn’t come right back up, and not being able to watch TV because your short-term memory problems mean you can’t follow a plot.

Maybe the real problem is that those of you who won’t even try to go to work on 2 hours sleep, and those who aren’t still working at midnight are lazy, and that’s why you choose to see that trait in me?

Monday, March 17, 2008

Most ME/CFS-patients have chronically activated immune systems, as is the case in Rheumatoid Arthritis patients. This problem is not detected in routine laboratory tests because these are mainly indicators for inflammation and do not reveal an altered 'innate immunity'. Nevertheless, there are laboratory tests available which indicate the presence of these maladjustments and which worsen under the influence of physical exertion. The parameters are: hCRP (high sensitivity CRP), elastase (index of immune activity), NO (nitric oxide) and presence in the serum of DNA, RNA, LPS (lipopolysaccharides), and/or antibodies for bowel bacteria in the blood.

If ME/CFS-patients are systematically examined for these markers, one finds that the majority of them have one or more abnormal values, and it is therefore probable that they will have a slow recovery after physical exercise. Furthermore, patients will sometimes feel worse after exertion because the underlying anomalies continue to become worse as a consequence of the physical exertion.

The case of nitric oxide (NO) is interesting. As a result of disruption in normal bowel flora in these patients, there is sometimes an increased NO-production by these bacteria. Also, due to an activated nonspecific immune system, the enzyme iNOS is responsible for higher NO-values in the serum. This, among other things, is responsible for a lowered blood pressure because it expands the larger blood vessels. As a result, the peripheral blood vessels must contract, which causes a maladapted circulation in different parts of the body.

Nitric monoxide, or simply NO, plays an important role in physical exertion. An acceleration of the heartbeat causes the blood flow to increase. As a response to this, endothelial cells trigger a number of processes to raise the production of NO. This leads to several processes which raise NO-production and activity and keep it going: the eNOS (endothelial enzyme that stimulates NO-production) becomes more active and there is a drop in the inactivation of NO caused by a decrease in production of free oxygen radicals and by activation of the anti-oxidizing ESA. NO is toxic for natural killer cells and T-cells because they lose their ability to function if there is too much NO circulating. This is one of the reasons why ME/CFS-patients easily become ill after they have engaged in physical activity.

Sports is beneficial to healthy individuals because NO has a protective impact against arteriosclerosis and bacterial infections. However, an excess of NO is detrimental and patients should be advised that physical exertion has been shown to lead to a build up of NO in people suffering from ME/CFS. Furthermore, these patients show exercise intolerance because the blood supply cannot adapt to the increased exercise-induced demand for oxygen in the tissues.

The case of NO is just one of the many imbalanced systems which create exercise intolerance and/or delayed recovery. Typically, an ME/CFS-patient of the Rheumatoid Arthritis type will have a much lower exercise capacity 24 hours after undergoing an exercise test till exhaustion. Also, a lot of patients do not reach their target heart rate when they are pushed to perform an exercise test, due to muscle weakness or pain in the lower extremities. This muscle weakness is a result of the binding of NO to the ryanodine receptors in the muscles. The pain is a result of maladapted blood flow in the muscles of the same extremities, which results in a premature accumulation of lactic acid. A portion of the NO will oxidize: NO + O2 -> ONOO - (peroxynitrate). This is a very strong free radical which damages cell membranes.

What can we learn from this?

ME/CFS-patients must never be forced to do compulsory exercise; they must listen to their bodies and not to other people who think they know better but are not familiar with the biology of these disorders.

Physical exercise must be adapted to the individual, based on the severity and consequences of the illness. Therefore, the individual patient evaluation should be extensive, specific and adapted to the disorder.

Researchers at the University of Michigan Health System have found a key linkagebetween pain and a specific brain molecule, a discovery that lends new insight into fibromyalgia, an often-baffling chronic pain condition.

In patients with fibromyalgia, researchers found, pain decreased when levels of the brain molecule called glutamate went down. The results of this study, which appears in the journal Arthritis and Rheumatism, could be useful to researchers looking for new drugs that treat fibromyalgia, the authors say.

"If these findings are replicated, investigators performing clinical treatment trials in fibromyalgia could potentially use glutamate as a 'surrogate' marker of disease response," says lead author Richard E. Harris, Ph.D., research assistant professor in the Division of Rheumatology at the U-M Medical School's Department of Internal Medicine and a researcher at the U-M Chronic Pain and Fatigue Research Center.

The molecule glutamate is a neurotransmitter, which means it conveys informationbetween neurons in the nervous system. When glutamate is released from one neuron, it diffuses across the space between cells, and then binds to receptorson the next neuron in line and causes the cell to become excited, or to be moreactive.

This molecule was suspected to play a role in fibromyalgia because previousstudies had shown that some brain regions in fibromyalgia patients appear to behighly excited. One such region is the insula.

In functional magnetic resonance imaging (fMRI) studies, researchers at U-M had previously shown that the insula displays augmented activity in fibromyalgia,which means neurons in these patients are more active in this part of the brain.The U-M team hypothesized, Harris notes, that more activity among these neuronsmight be related to the level of glutamate in this region.

To gauge the linkage between pain and glutamate, the researchers used a non-invasive brain imaging techinique called proton magnetic resonance spectroscopy(H-MRS). H-MRS was performed once before and once following a four-week courseof acupuncture or "sham" acupuncture.

Researchers used either acupuncture or sham acupuncture to reduce pain symptoms.The sham procedure involved using a sharp device to prick the skin in order tomimic real acupuncture sensations.

Following the four weeks of treatment, both clinical and experimental painreported were reduced significantly. More importantly the reduction in both painoutcomes was linked with reductions in glutamate levels in the insula: patientswith greater reductions in pain showed greater reductions in glutamate. Thissuggests that glutamate may play a role in this disease and that it couldpotentially be used as a biomarker of disease severity.

Because of the small number of participants in this study, further researchshould be conducted to verify the role of glutamate in fibromyalgia, Harrissays.

The senior author of the study was Daniel J. Clauw, M.D., director of the U-M Chronic Pain and Fatigue Research Center. Other authors were Richard H. Gracely, Ph.D., and Seong-Ho Kim, M.D., of the U-M Department of Internal Medicine; Pia C. Sundgren, M.D., Ph.D., Yuxi Pang, Ph.D., and Myria Petrou, M.D., of the U-M Department of Radiology; Michael Hsu, M.D., of the U-M Department of Physical Medicine and Rehabilitation; and Samuel A. McLean, M.D., of the U-M Department of Emergency Medicine.

Funding came from a Department of Army grant, the National Institutes of Health, and the NIH National Center for Complementary and Alternative Medicine.

Reference: Arthritis and Rheumatism, March 2008, Volume 58, Issue 3, "Dynamic Levels of Glutamate within the Insula are Associated with Improvements in Multiple Pain Domains in Fibromyalgia."